Acute Fibrinous and Organizing Pneumonia (AFOP) in Children: A Case Report and Literature Review

Introduction

Acute Fibrinous and Organizing Pneumonia (AFOP) is a rare histopathological entity that presents with acute lung injury characterized by intra-alveolar fibrin deposition.¹ Unlike other interstitial lung diseases, AFOP lacks the classical hyaline membranes seen in diffuse alveolar damage, making its diagnosis more challenging. Although primarily described in adults, AFOP has been reported across various age groups, including the pediatric population, where it remains under-recognized.^1,2

The etiologies of AFOP are diverse and can include connective tissue diseases, infections, occupational exposures, drug reactions, and autoimmune disorders.¹ In many cases, the underlying cause is not immediately apparent, leading to a delay in diagnosis and appropriate treatment.³ The clinical presentation of AFOP is often nonspecific, with symptoms such as cough, fever, and dyspnea, which can mimic common respiratory illnesses, further complicating the diagnosis.⁴

In this report, we present a pediatric case of AFOP that initially manifested as recurrent viral-induced wheezing, a condition commonly mistaken for asthma or other benign respiratory disorders in children.⁴ Through comprehensive clinical evaluation, including histopathological examination, the diagnosis of AFOP was established, highlighting the importance of considering this rare condition in pediatric patients with atypical respiratory presentations.

Methods and Materials

This case report documents the clinical presentation, diagnostic process, and management of a unique and instructive pediatric respiratory case encountered in clinical practice. The patient’s data were collected retrospectively from medical records, including clinical notes, laboratory results, imaging studies, and histopathological findings, where applicable. All procedures and interventions involving chest x-ray, chest CT scan, Lung biopsy and bronchoscopy, were conducted in accordance with standard clinical protocols and ethical guidelines. Informed written consent was obtained and signed from parents of the child for the use of his medical information for educational and publication purposes, ensuring confidentiality and anonymity.

Result

A 3-year-old boy, born at term, presented with a history beginning at the age of 2 years when he developed an upper respiratory tract infection. This infection progressed to an asthma-like exacerbation characterized by wheezing and dry cough, which responded partially to bronchodilators. Since then, he has experienced recurrent exacerbations, mostly triggered by viral illnesses. Upon referring the patient to us, he had persistent hypoxemia and required supplemental home oxygen.

The mother reported no history of recurrent chest or ear infections, persistent rhinorrhea, year-round wet cough, oily stools, obstructive sleep apnea-related symptoms, choking or aspiration episodes, or worsening symptoms with bronchodilators. He has food allergies to nuts, specifically cashews and pistachios. The family has a strong history of atopy on both the paternal and maternal sides. There is a history of infertility from the maternal side. There is no family history of cystic fibrosis, immunodeficiency, or autoimmune disorders.

On initial physical examination, the child was comfortably lying in bed, receiving 1 liter of oxygen via nasal cannula and maintaining an oxygen saturation of 92% or higher. Chest examination revealed decreased air entry in the right upper and middle zones without wheezes or other abnormal sounds. Systemic assessment did not reveal any other abnormalities. A chest X-ray (Figure 1) showed segmental consolidative opacity in the right upper lobe, which was also present on his previous chest X-rays. Complete Blood Count (CBC), Rheumatological, immunological and genetic workups were all unremarkable.

Figure 1 Chest X-ray: There is a right upper zone airspace opacity with an air bronchogram, suggestive of consolidation.

Given the patient’s chronic symptoms and persistent radiological findings, a high-resolution computed tomography (HRCT) scan (Figure 2) was conducted. It revealed consolidation of the entire right upper lobe and a small part of the right middle lobe, along with scattered tiny lung nodules and diffuse mosaic lung attenuation likely related to air trapping. Bronchoscopy revealed normal airway anatomy with thick yellowish secretions throughout, particularly in the right upper lobe; no foreign body was detected. His bronchoalveolar lavage (Table 1) culture tested positive for Haemophilus influenzae and showed leukocytosis with a neutrophil-predominant profile (82%). Targeted antimicrobial treatment was administered; however, he did not achieve radiographic clearance of the airspace opacities in the right upper and middle zones.

Table 1 Bronchoalveolar Lavage (BAL) Findings

Figure 2 HRCT Chest: (A) There is a consolidation of the right upper lobe. (B) Diffuse bilateral ground-glass opacities and scattered tiny lung nodules.

Subsequently, an open lung biopsy was performed, which was suggestive of Acute Fibrinous and Organizing Pneumonia (AFOP). The biopsy showed a focal area of AFOP associated with mild chronic bronchiolitis and was negative for granulomas, vasculitis, viral inclusions, and malignancy (Figure 3). He was started on steroid treatment with prednisolone at a dose of 1 mg/kg daily, which was gradually tapered down to over the next 6 months. Azithromycin has been started as an anti-inflammatory adjuvant therapy. He no longer experiences frequent episodes of his prior respiratory symptoms, requiring only occasional administration of salbutamol for symptomatic relief. He has not required supplemental oxygen for over six months, and his oxygen saturation levels have normalized. Follow-up chest X-ray showed a significant improvement of the right upper lobe consolidation, which had persisted for a year prior (Figure 4).

Figure 3 Lung biopsy: (A) Focal area of acute fibrinous organizing pneumonia (AFOP) (B) Associated with mild chronic bronchiolitis. Both are Negative for granuloma, vasculitis, viral inclusions, and malignancy.

Figure 4 Chest x-ray: The follow up chest x-ray showed peri bronchial thickening with significant improvement in the right upper lobe opacity.

Discussion

Acute Fibrinous and Organizing Pneumonia (AFOP) was first described by Beasley et al, who reported 17 adult patients with acute symptoms resembling organizing pneumonia.⁵ However, AFOP has its own distinct histopathology characterized by intra-alveolar fibrin in the form of fibrin “balls” in patchy distributions, along with mild-to-moderate lymphoplasmacytic infiltrates. The disease predominantly affects adults, with few cases reported in the pediatric population.^6,7 The first reported case of AFOP in children was by Prahalad et al, who described a 14-year-old girl with juvenile dermatomyositis who later developed AFOP.⁸ Since then, only a few cases have been reported in the pediatric population, each contributing valuable insights into AFOP in children.^6–11

The etiology of AFOP in reported pediatric cases includes juvenile dermatomyositis, acute respiratory distress syndrome (ARDS), hypersensitivity pneumonitis, immune dysregulation, and drug-induced lung injury, such as from trimethoprim-sulfamethoxazole.^6–11 In contrast, our case might be idiopathic or might be induced by bacterial infection, specifically Haemophilus influenzae, which is a known infectious association of AFOP.^12,13 Clinically, these patients presented with a range of respiratory symptoms, including cough, dyspnea, fever, pleuritic chest pain, and wheezing, all of which were observed in our case as well. In some instances, patients with AFOP have also presented with pleural effusions and, very rarely, pneumothorax.^2,6,12,14 The symptoms of AFOP can closely mimic those of community-acquired pneumonia or recurrent viral-induced wheeze, posing a diagnostic challenge.

Radiologically, pediatric AFOP is typically characterized by consolidation and diffuse ground-glass opacities, with additional findings in this case that include pleural effusion, nodules, halo sign, and air-leak syndromes.^6,15,16 Notably, these radiological manifestations are similar to those observed in adult AFOP patients, underscoring the consistent presentation of the disease across different age groups.^5,15 However, it is important to note that no distinct radiological features are pathognomonic for AFOP, and thus, imaging alone cannot confirm the diagnosis. Diagnosis is generally established through lung biopsy, which demonstrates intra-alveolar fibrin in the form of “fibrin balls” and varying degrees of organizing pneumonia. In contrast to diffuse alveolar damage seen in other interstitial lung diseases, AFOP is distinguished by the absence of hyaline membranes and a paucity of neutrophilic infiltration.^4,5,12,14

At present, the treatment of AFOP remains non-standardized, and therapeutic approaches continue to be evaluated. The management generally involves addressing the underlying condition, with corticosteroids serving as the cornerstone of therapy. However, patient responses and outcomes are highly variable. There have been multiple reports in the literature suggesting that AFOP may exhibit a modest response to corticosteroid and immunosuppressive therapies.^4,17,18 In particular, patients with underlying connective tissue disorders or autoimmune diseases appear to derive the most benefit from immunosuppressive agents.^7,18 Mycophenolate mofetil and cyclophosphamide have been recommended by some authors as adjunctive treatments in such cases.^17,18 In our patient, azithromycin was utilized as an immune modulator, a therapeutic approach that, to our knowledge, has not been previously reported in the management of AFOP.

Conclusion

AFOP remains a rare and challenging diagnosis, particularly in the pediatric population, where the clinical and radiological findings can easily mimic other pulmonary conditions. Lung biopsy remains the definitive diagnostic tool, given the lack of distinct radiological features. While corticosteroids and immunosuppressive therapies are currently the mainstay of treatment, their efficacy varies widely, necessitating individualized therapeutic approaches. Our use of azithromycin as an immune modulator represents a novel intervention in the treatment of pediatric AFOP, warranting further investigation. Continued case reporting is critical to enhance understanding of this rare disease and to establish more effective, evidence-based treatment protocols.